Early detection of pediatric cancer thanks to artificial intelligence
Discover how THALES collaborates with the CNRS to identify new genetic markers leading to the development of pediatric cancers, thereby contributing to the improvement of patient care.
Pediatric cancer and social issue
In southern Brazil, several cases of adrenocortical carcinoma (ACT) in children under 5 are recorded every year. This rare disease, which often carries a poor prognosis, is in an aggressive form of cancer affecting the endocrine system. ACT is 15 times more prevalent in southern Brazil than anywhere else in the world. In addition to the difficulties inherent to standard oncological follow-ups, children with ACT may present, according to their sex, symptoms of precocious puberty such as body hair, acne, developed sex organs or menstrual periods. Surgical removal of the tumor remains the mainstay of treatment, offering the best chance for a cure. However, for many patients, the diagnosis comes too late: tumors detected at an advanced stage are often inoperable, and metastatic processes may have already taken place. In such cases, the therapeutic alternatives are limited and the chances of survival are greatly reduced. Early detection is key in the fight against this cancer.
Industrial and academic research partnership
For over a century, Hospital Pequeno Príncipe in Curitiba (State of Paraná) has been offering specialized health care services to children. This non-profit establishment is currently recognized as one of the best pediatric hospitals in the world. It is home to Pelé Pequeno Príncipe Research Institute, where Prof. Bonald Figueiredo and his team, in collaboration with Dr. Enzo Lalli of the CNRS Institute of Molecular and Cellular Pharmacology (IPMC), have observed a strong presence, for the local population, of a specific mutation. This p.R337H mutation located on the TP53 gene deteriorates its tumor suppressing function. Since only a small percentage of carriers of this mutation develop ACT, these researchers strive to identify other genetic and environmental factors driving tumor onset. The goal is to ensure early detection and monitoring of individuals at risk. THALES has mobilized its data scientists and technical infrastructure since 2022, to support Dr. Enzo Lali and Dr. Bonald Figueiredo in the search for such genetic factors.
Technical solution: AI for genomic analysis
The originality of Thales’s work lies in the use of a database made up of trios, i.e. genetic sequencing of father-mother-child families. Within each family, both parents are healthy, but only one of them carries the mutated TP53 p.R337H gene. In turn, all children in the studied sample carry the mutation – some having developed the disease, while others compose the control group.
THALES has developed an artificial intelligence framework which allows the identification of candidate activating and protective genes involved in the disease pathway. The procedure considered the parent-child association and was based on the application of frequency and heritability analysis tools, as well as other state-of-the-art techniques. These results were used in the development of an indicator measuring the likelihood the ACT onset, or Polygenic Risk Score (PRS), specifically tailored for this disease. The methodology is currently undergoing validation procedures in the target population and could eventually enable the large-scale testing of individuals at risk at a much lower cost than that of a complete sequencing, making way to individualized monitoring from birth. If confirmed, the results obtained can represent a major advancement in the early detection of this cancer.
Towards the future: preventive and personalized medicine
The Genome Analyzer is a pioneering THALES initiative in the field of preventive and personalized medicine. This project, which shows the value of collaboration between clinicians, biomedical researchers and data scientists, was presented in the international colloquium, «The II Workshop on past, present and future of pediatric adrenocortical tumor research », hosted in Brazil between March 13 and 15, 2023. The event brought together some of ACT's leading specialists, including experts from St. Jude Children's Research Hospital (Memphis, TN, USA) the world's leading center for pediatric oncology. The entire framework developed for this project, with a potential for generalization, could be extended to other pathologies, broadening Thales’s solutions in the field of health and serving as an accelerator for new projects.